Petrelintide

Petrelintide (ZP8396) is an investigational amylin analog being developed by Zealand Pharma and Roche as a once-weekly injectable for weight management. It works differently from GLP-1 drugs like semaglutide, targeting amylin receptors to restore satiety and leptin sensitivity rather than suppressing appetite through the incretin pathway. In its phase 2 trial, it produced up to 10.7% mean weight loss over 42 weeks with a side-effect profile close to placebo, notably almost no vomiting. It has never been approved anywhere and has never been sold, legitimately or otherwise; phase 3 trials (the ZUPREME program) began September 22, 2026.

Research snapshot

Peptide category	Amylin analog (dual amylin/calcitonin receptor agonist)
Primary research interest	Chronic weight management in overweight/obesity
Highest available evidence	Published Phase 1 human trial data; Phase 2 topline and congress data (not yet full-text published); Phase 3 recruiting
Human research available	Yes — Phase 1 (published), Phase 2 (company-reported, congress-presented), Phase 3 (in progress)
Development status	Phase 3 (ZUPREME-3, -4, -5 registrational program, initiated September 2026)
Regulatory status	Not approved anywhere. Not sold under any legitimate channel.
Last reviewed	September 27, 2026

Technical identity

Primary name	Petrelintide
Alternative names	ZP8396
Peptide sequence	Not published in a primary source as of this review
Amino-acid length	Not reliably established from public sources
Molecular formula	Conflicting: PubChem lists two separate compound records — one gives C185H305N49O61 (CID 172915807), the other, listed as “Petrelintide (ZP8396),” gives C184H302N48O61 (CID 176451455). The one-atom difference is not resolved in the public record reviewed.
Molecular weight	Not stated in a source independently verifiable beyond the conflicting PubChem records above
CAS Registry Number	2766385-23-1, per a commercial vendor listing; not independently cross-confirmed against a regulatory database
PubChem CID	Conflicting — see molecular formula row
UNII	Not reliably established
DrugBank ID	Not listed
Chemical modifications	Described by the developer as engineered for chemical and physical stability with no fibrillation at neutral pH, allowing co-formulation with other peptides
Peptide class	Long-acting amylin receptor agonist
Primary biological target	Amylin receptor (with calcitonin receptor activity in some vendor/database labeling — “DACRA”)
Developer or originator	Zealand Pharma (Denmark); co-developed and co-commercialized with Roche/Genentech under a March 2025 global agreement
Development status	Phase 3

What is petrelintide?

Petrelintide, known in earlier trials by its code name ZP8396, is an investigational long-acting analog of amylin, a hormone the pancreas releases alongside insulin after eating. It is being developed jointly by Zealand Pharma, the Danish peptide company that also created cagrilintide, and Roche, which licensed global rights to co-develop and sell it in March 2025.

Where most of the current obesity-drug conversation centers on GLP-1 receptor agonists like semaglutide and tirzepatide, petrelintide belongs to a different, smaller class: pure amylin analogs. Amylin’s job in the body is to slow gastric emptying and signal fullness to the brain, and it does this partly by restoring the brain’s sensitivity to leptin, the hormone that normally tells the body it has enough fat stored. That distinction is the whole reason petrelintide exists as its own program rather than being folded into Zealand’s GLP-1/amylin combination work, as it is with cagrilintide and semaglutide in CagriSema.

Petrelintide first appeared in the clinic in a pair of phase 1 trials (single and multiple ascending dose), then moved into a 493-person phase 2 trial (ZUPREME-1) that read out in March 2026, with more detailed data shown at the American Diabetes Association’s June 2026 meeting. A second phase 2 trial in people with type 2 diabetes, ZUPREME-2, is expected to report in the second half of 2026. On September 22, 2026, Zealand announced the drug had moved directly into a three-trial, roughly 7,000-person phase 3 registrational program (ZUPREME-3, -4, and -5), aimed at supporting a future marketing application for petrelintide as a standalone weight-management drug. It has never been approved for any use, in any country, and it has never been available for purchase through any channel, legitimate or otherwise.

How does it work?

Plain-English explanation

Amylin is a hormone your pancreas normally releases at the same time as insulin, right after you eat. Its job is to slow down how fast food leaves your stomach and to tell your brain you’re full. Petrelintide is a lab-made, longer-lasting version of that hormone, redesigned so one injection a week can do the job amylin normally does meal by meal.

The part that makes petrelintide interesting to researchers isn’t just that it curbs appetite. Amylin signaling also appears to make the brain more responsive to leptin, the hormone that reports how much fat the body is carrying. In obesity, that leptin signal often gets ignored, a state researchers call leptin resistance. If restoring amylin signaling helps the brain “hear” leptin again, that’s a mechanically different way of losing weight than simply dialing down appetite the way GLP-1 drugs do, which is why Zealand and Roche are positioning this less as another GLP-1 alternative and more as a genuinely separate approach.

Technical explanation

Petrelintide is a long-acting amylin receptor agonist engineered for once-weekly subcutaneous dosing, in contrast to native human amylin’s half-life of only a few minutes. Public developer material describes the molecule as chemically and physically stable, with no fibrillation, a tendency of amylin-family peptides to clump together, at neutral pH, a stability profile Zealand says permits co-formulation and co-administration with other peptide drugs. Its receptor pharmacology is described in some vendor and database listings as a “dual amylin/calcitonin receptor agonist” (a DACRA), a class that includes davalintide and, like cagrilintide, may retain some calcitonin receptor activity alongside amylin receptor activation, though petrelintide’s precise receptor selectivity profile relative to cagrilintide has not been published in a peer-reviewed pharmacology paper as of this review. Full pharmacokinetic parameters from the phase 1 program are reported in the published phase 1 paper (Braendholt Olsen et al., Diabetes, Obesity and Metabolism, 2026) but were not independently re-extracted beyond what is cited below.

Potential benefits and research applications

Weight loss in people with overweight or obesity

This is the entire reason petrelintide exists as a program. In the phase 2 ZUPREME-1 trial (493 participants, mean BMI 37, 42 weeks), petrelintide produced up to 10.7% mean weight loss versus 1.7% with placebo (p<0.001) at week 42, with a statistically significant effect already visible by week 28 across all five dose arms tested. Female participants lost considerably more weight than male participants in the trial, a difference the company has not yet fully explained. Evidence: has been shown in a randomized, placebo-controlled phase 2 human trial (company-reported and presented at a medical congress; full peer-reviewed publication of the phase 2 results was not identified as of this review, so the specific percentages should be treated as company-reported pending journal publication).

Tolerability advantage over other injectable weight-loss drugs

The headline finding researchers and analysts have focused on isn’t the weight-loss number itself, which is broadly in line with cagrilintide, but how well it was tolerated. In the phase 2 trial, there was no vomiting at all in the maximally effective dose arm, nausea rates were lower than in the earlier phase 1b trial, and diarrhea and constipation stayed in the single digits. Treatment discontinuation due to side effects was 4.8% on petrelintide versus 4.9% on placebo, statistically indistinguishable, and overall trial withdrawal was actually lower on petrelintide (8.4%) than on placebo (13.6%). Evidence: has been reported in company/congress-presented phase 2 trial data; the phase 1 program’s GI tolerability data is published in a peer-reviewed journal.

Combination potential with GLP-1/GIP drugs

Zealand has stated a phase 2 combination trial pairing petrelintide with CT-388 (Roche/Genentech’s own GLP-1/GIP dual agonist, also known as enicepatide) is planned to start later in 2026. The rationale, not yet tested in a completed human trial, is that combining an amylin-pathway drug with an incretin-pathway drug could produce weight loss beyond what either drug achieves alone, following the same logic behind CagriSema. Evidence: is being investigated for (registered but not yet recruiting/completed trial); has not been established, since the combination trial has not reported any data.

What dosage information circulates?

Figures in this section summarize amounts and schedules reported in published research or company disclosures. Their inclusion documents what is reported and does not establish that a regimen is verified, safe, effective, or appropriate. Petrelintide has never been sold under any brand or research-chemical name. There is no vendor, forum, or community dosage to report, and any product sold online today claiming to be petrelintide is not genuine, since the molecule does not exist outside sponsor-controlled clinical trial supply.

The published phase 1 program tested ascending subcutaneous doses across multiple cohorts, single-dose and weekly multiple-dose, over up to 16 weeks, though specific per-cohort milligram amounts were not independently re-extracted from the paper for this page. The phase 2 ZUPREME-1 trial used five weekly subcutaneous dose arms with a 12-week step-up period followed by maintenance to week 42, but the specific per-arm doses were not disclosed in the press materials reviewed. The ongoing phase 3 trials, ZUPREME-3 and -4 (weight management, with and without type 2 diabetes, 12-week escalation, maintenance to week 64, follow-up to week 77) and ZUPREME-5 (weight management with cardiovascular disease, up to three years), all dose once weekly by subcutaneous injection, but exact amounts have not yet been disclosed.

No community, forum, or vendor dosage figure exists for petrelintide, and that absence is itself the important fact for this section rather than an oversight. Unlike a compound such as BPC-157 or even retatrutide, petrelintide has no synthesis pathway that has reached the grey-market peptide supply chain; it is structurally complex, patent-protected, and still inside a sponsor-controlled clinical trial supply chain with a few hundred total human exposures worldwide as of this review. Every dose number that exists comes from Zealand Pharma’s or Roche’s own trial disclosures, and the specific milligram amounts used in each dose arm have not been made public in the press releases and abstracts reviewed for this page; that level of detail typically appears only in the full peer-reviewed publication or a regulatory filing package, neither of which exists yet for petrelintide.

Reported use or research objective	Route reported	Amount reported	Frequency reported	Reported duration	Evidence or source category
Phase 1 SAD/MAD safety and tolerability	Subcutaneous	Ascending doses across multiple cohorts; specific mg amounts not independently re-extracted	Single dose (SAD) / weekly (MAD)	Up to 16 weeks (MAD part 2)	Published human clinical trial (PMID 42017294)
Phase 2 ZUPREME-1, weight management (no diabetes)	Subcutaneous	Five dose arms with 4-week step-ups; specific per-arm mg doses not disclosed	Once weekly	42 weeks (12-week escalation + maintenance)	Company-reported, congress-presented human trial
Phase 3 ZUPREME-3/-4, weight management ± type 2 diabetes	Subcutaneous	Not yet disclosed	Once weekly	12-week escalation, maintenance to week 64, follow-up to week 77	Registered human trial, ongoing
Phase 3 ZUPREME-5, weight management with cardiovascular disease	Subcutaneous	Not yet disclosed	Once weekly	Up to 3 years	Registered human trial, ongoing
Practitioner or community protocols	—	—	—	—	Not consistently reported — no established or reliably sourced dosing information exists outside sponsor trials; petrelintide has never been sold anywhere

Side effects, risks, and limitations

Reported so far, exclusively from company-sponsored phase 1 and phase 2 trials: nausea, present but reported at rates the company describes as lower in phase 2 than in the earlier phase 1b trial, and comparable to placebo in some cohorts; no vomiting reported in the phase 2 trial’s maximally effective dose arm, and rare in phase 1; diarrhea and constipation in the single digits of participants in phase 2; and discontinuation for adverse events of 4.8% (petrelintide) versus 4.9% (placebo) in phase 2, not meaningfully different from placebo, which is the headline tolerability finding driving analyst interest in this drug.

What is not yet known: long-term safety beyond the current trial durations (the longest disclosed so far is the up-to-three-year ZUPREME-5 cardiovascular trial, still ongoing); safety in pregnancy; interactions with other drugs; safety or effect size in adolescents; and any signal specific to the male-versus-female weight-loss difference seen in phase 2. Because petrelintide has never been sold outside sponsor-controlled trials, there is no purity, contamination, or mislabeling concern to report the way there is for compounds that circulate through the grey-market research-chemical supply chain; the risk profile here is entirely about the unfinished clinical evidence, not product-quality risk.

Regulatory and developmental status

Petrelintide is not approved for any use in any country. It is in phase 3 (registrational) clinical development, the stage intended to generate the evidence needed for a future marketing application, following Zealand Pharma’s own description of the ZUPREME-3/-4/-5 program’s purpose. No regulatory filing has been submitted or announced as of this review (September 26, 2026), and no timeline for one has been disclosed publicly. Development is being run jointly by Zealand Pharma (Denmark) and Roche/Genentech under their March 2025 collaboration agreement.

Frequently asked questions

What is petrelintide?

Petrelintide (also known by its earlier code name ZP8396) is an investigational amylin analog being developed by Zealand Pharma and Roche for weight management, currently in phase 3 trials.

How does petrelintide work?

It mimics amylin, a hormone your pancreas releases after eating, to increase feelings of fullness and help restore the brain’s sensitivity to leptin, a mechanism distinct from GLP-1 drugs like semaglutide.

What dosage has been studied?

Specific milligram doses from the phase 1, 2, and 3 trials have not been publicly disclosed in the sources reviewed here. Dosing is once weekly by subcutaneous injection with a multi-week escalation period, consistent across all disclosed trials.

What dosage commonly circulates online?

None. Petrelintide has never been available for purchase anywhere, legitimately or otherwise; it exists only inside sponsor-controlled clinical trials.

Has petrelintide been studied in humans?

Yes. Published phase 1 data exists, phase 2 has reported topline and congress-presented results, and phase 3 began in September 2026.

Is petrelintide approved?

No. It has not been approved anywhere, and it is not legally available for sale under any circumstance.

How does petrelintide compare to cagrilintide?

Both are Zealand Pharma amylin analogs. Cagrilintide is further along commercially, combined with semaglutide as CagriSema, which was rejected on a head-to-head endpoint against tirzepatide in the REDEFINE 4 trial in February 2026, and further along as a monotherapy candidate. Petrelintide is newer, positioned specifically on tolerability, and has reported a cleaner GI side-effect profile in its own trials than cagrilintide’s published monotherapy data, though the two drugs have not been tested head-to-head.

What remains unknown?

Long-term safety and durability of weight loss beyond current trial durations, the specific doses used in each trial arm, the reason for the male/female weight-loss difference seen in phase 2, and whether the CT-388 combination trial will show additive benefit.

Bottom line

Petrelintide is one of the most closely watched amylin-analog candidates in the obesity pipeline right now, not because its weight-loss numbers are dramatically better than cagrilintide’s, but because its phase 2 tolerability data, essentially placebo-level discontinuation and no vomiting in its best-performing dose arm, is the strongest GI safety signal reported for any amylin drug in this class to date. It just entered phase 3 as a registrational program on September 22, 2026, days before this page was written, so what is published is still limited: solid phase 1 pharmacokinetics, promising but not-yet-peer-reviewed phase 2 efficacy and safety data, and a large ongoing phase 3 program with no results yet. It has never been approved and has never been sold anywhere, and there is no dosage information beyond what sponsors have disclosed for their own trials.